Adult Pseudomonas aeruginosa Meningitis High Incidence of Underlying by tpf49254

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									Jpn. J. Infect. Dis., 60, 397-399, 2007


  Short Communication
      Adult Pseudomonas aeruginosa Meningitis: High Incidence of Underlying
       Medical and/or Postneurosurgical Conditions and High Mortality Rate
                      C. R. Huang, C. H. Lu, Y. C. Chuang, N. W. Tsai, C. C. Chang, S. F. Chen,
                                    H. C. Wang1, C. C. Chien2 and W. N. Chang*
             Department of Neurology, 1Department of Neurosurgery and 2Department of Diagnostic Pathology,
              Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of
                                             Medicine, Kaohsiung, Taiwan
                                     (Received June 25, 2007. Accepted August 15, 2007)
       SUMMARY: We analyzed the clinical and laboratory characteristics, therapeutic outcome and prognostic factors
       of 25 cases of cerebrospinal fluid (CSF) culture-proven Pseudomonas aeruginosa adult bacterial meningitis
       (ABM). Twelve P. aeruginosa strains, isolated from clinical CSF specimens, were tested for antibiotic suscep-
       tibility. The 25 cases included 17 men and 8 women, aged 17 to 86 years (median = 51). Of the 25 cases of P.
       aeruginosa ABM, 18 were the result of postneurosurgical infection and the other 7 were spontaneous infections.
       The latter 7 cases had serious underlying medical conditions. The antibiotic susceptibility rates of the 12 strains
       were as follows: ceftriaxone 16.7% (2/12), ceftazidime 91.7% (11/12), cefepime 83.3% (10/12), imipenem 83.3%
       (10/12), meropenem 83.3% (10/12) and ciprofloxacin 66.7% (8/12). The therapeutic results showed an overall
       mortality rate of 40% (10/25). The emergence of third-generation cephalosporin-resistant P. aeruginosa strains
       cultured from clinical CSF specimens in recent years has resulted in a therapeutic challenge in the treatment of
       ABM.

   In both eastern and western countries, Pseudomonas                   ceftriaxone, ceftazidime, cefepime, imipenem, meropenem
aeruginosa is not a common pathogen of bacterial meningitis             and ciprofloxacin.
(1,2). Although large-scale studies of overall adult bacterial             For comparative analysis, the 25 P. aeruginosa ABM cases
meningitis (ABM) have been conducted (1,2), P. aeruginosa               were divided into two groups (fatal and non-fatal groups).
as a sole cause for ABM has been rarely examined in the                 Data including gender, type of acquisition of infection, type
literature. In this study, we analyzed the clinical and labo-           of infection, underlying conditions, clinical manifestations
ratory features and the therapeutic outcomes of 25 mono-                and therapeutic outcomes between these two patient groups
microbial P. aeruginosa ABM cases. We also examined the                 were analyzed by means of a chi-square test or Fisher’s exact
antimicrobial susceptibility of 12 P. aeruginosa strains                test. The age difference between the two patient groups was
isolated from clinical cerebrospinal fluid (CSF) specimens.             analyzed by means of Student’s t test. The consciousness lev-
   During the study period (21 years, 1986 - 2006), 392 adult           els of the two groups at the time of admission were analyzed
patients ( 17 years old) were determined to have culture-               by means of the Mann-Whitney test. CSF data for the leuko-
proven bacterial meningitis. Of these 392 cases, 350 had                cyte counts, glucose, total proteins and lactate concentrations
monomicrobial infections while the other 42 had poly-                   were logarithmically transformed to improved normality, and
microbial infections. Of the 350 cases with monomicrobial               comparisons were made using Student’s t test. All analysis
infections, 29 cases had Pseudomonas ABM, and 25 of these               was conducted using SAS (SAS Statistical Institute, Cary,
29 cases were cases of P. aeruginosa infection. The others              N.C., USA).
were Pseudomonas mendocina (n = 2) and Pseudomonas                         The clinical and laboratory data of the 25 P. aeruginosa
stutzeri (n = 1), while one was not subtyped. Of the 42 cases           ABM cases are listed in Tables 1 and 2. The underlying con-
of mixed infections, 12 involved Pseudomonas infection, and             ditions of the seven cases with spontaneous infection were
all 12 of these were P. aeruginosa. The criteria for a definite         systemic lupus erythematosus (SLE) (n = 1), otitis medium
diagnosis of P. aeruginosa meningitis included the follow-              (n = 1), lung cancer with liver metastasis (n = 1), alcoholism
ing: (i) a positive CSF culture of P. aeruginosa, (ii) clinical         with liver cirrhosis (n = 1), P. aeruginosa pneumonia with
features of meningitis and (iii) purulent CSF features. The             respiratory failure (n = 1), diabetes mellitus (DM) with SLE
antibiotic susceptibility of the 12 isolated P. aeruginosa              with end-stage renal disease (ESRD) (n = 1) and DM with
strains was tested using the Kirby-Bauer diffusion method               ESRD (n = 1). In the 18 cases with a preceding neurosurgical
(BBL, Muller-Hinton II agars; Becton Dickinson Micro-                   state, the median time lag between the last neurosurgical pro-
biology Systems, Cockeysville, Md., USA) as described in                cedure and the diagnosis of P. aeruginosa ABM was 20 days
the Clinical and Laboratory Standards (CLSI) guidelines for             (3 - 720 days). The CSF data, as shown in Table 1, revealed
MICs. The antibiotics used in the susceptibility test included          the features of purulent inflammation. The results of the anti-
                                                                        microbial susceptibility tests are listed in Table 3. Overall,
  *Corresponding author: Mailing address: Department of Neurol-         10 of the patients died and 15 survived, and only the differ-
   ogy, Chang Gung Memorial Hospital-Kaohsiung, 123 Ta Pei              ence in the level of the CSF leukocyte counts between the
   Road, Niao Sung Hsiang, Kaohsiung Hsien 833, Taiwan.                 fatal and non-fatal groups was of statistical significance.
   Tel: +886-7-7317123 ext. 2283, Fax: +886-7-7333816, E-mail:          Six of the 12 cases whose CSF-isolated P. aeruginosa strains
   cwenneng@ms19.hinet.net                                              were used in the antibiotic susceptibility test died. The major

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                           Table 1. Underlying medical conditions of the 25 adult Pseudomonas aeruginosa meningitis cases
                                                            Non-fatal                  Fatal
                                                                                                          OR             95% CI        P-value
                                                             n = 15                   n = 10
                Age at meningitis (y)                       39.9±18.3                53.3±20.9                                          0.328
                Gender
                  Female                                         5                       3             0.857        0.152 - 4.819       1
                  Male                                          10                       7
                Clinical feature
                  Fever                                         11                       8             0.917        0.123 - 6.825       1
                  Disturbed consciousness 1)                    11                       8             0.688        0.1 - 4.719         1
                  Seizure                                        7                       4             1.313        0.259 - 6.643       1
                  Septic shock                                   0 3)                    1             0.375        0.224 - 0.629       0.4
                  Hydrocephalus                                  7                       4             1.313        0.259 - 6.643       1
                  CSF leakage                                    0 3)                    1             0.375        0.224 - 0.629       0.4
                Acquisition of infection
                  Community acquired                             5                       3             1.167        0.208 - 6.559       1
                  Nosocomial acquired                           10                       7
                Types of infection
                  Spontaneous meningitis                         4                       3             0.848        0.144 - 4.99        1
                  Postneurosurgical meningitis                  11                       7
                Underlying medical disorders
                  Diabetes mellitus                              5                       3             1.167        0.208 - 6.559       1
                  Alcoholism                                     1                       1             0.643        0.036 - 11.631      1
                  End-stage renal disease                        1                       1             0.643        0.036 - 11.631      1
                  Systemic lupus erythematosus                   1                       2             0.286        0.022 - 3.669       0.543
                  Malignancy                                     1                       1             0.643        0.036 - 11.631      1
                Peripheral blood study
                  Bacteremia                                     3                       5
                  Leukocytosis 2)                               11                       8             0.688        0.1 - 4.719         1
                CSF data
                  Glucose (mmol/L)                     2.53 (0.06 - 8.21)       0.60 (0.22 - 6.50)                                      0.403
                  Total protein (g/L)                  1.61 (0.19 - 27.59)      3.80 (1.18 - 6.45)                                      0.295
                  Lactate (mmol/L)                     6.42 (0.22 - 21.70)     12.65 (2.79 - 23.43)                                     0.158
                  Leukocyte count ( 106/L)             0.14 (0.003 - 15.8)      0.85 (0.29 - 3.78)                                      0.024
                1)
                  : Glasgow coma scale <15.
                2)
                  : Leukocyte count > 10 109/L.
                3)
                  : Using a correction of 0.5 in every cell that contains a zero.


 Table 2. Preceding neurosurgical events of the 18 adult Pseudomonas                  Table 3. Results of antibiotic susceptibility tests of 12 Pseudomonas
   aeruginosa meningitis cases                                                          aeruginosa strains
   Traumatic skull fracture and subarachnoid hemorrhange (SAH) (1)                                         Susceptible test               MICs (mg/dL)
                                                                                    Antimicrobial agent
   Traumatic skull fracture (1)                                                                              S I R                  Breakpoint MIC50 MIC90
   Traumatic subdural hemorrhage (SDH) + SAH
                                                                                       Ceftriaxone              2    2     8          ≤8         64     128
      + ventriculoperitoneal (VP) shunt (1)
                                                                                       Ceftazidime             11    0     1          ≤8          4       8
   Traumatic intracerebral hemorrhage (ICH) + SAH + SDH
      + craniectomy (1)                                                                Cefepime                10    1     1          ≤8         16       8
   Traumatic epidural hemorrhage (EDH) + SDH + craniotomy (1)                          Imipenem                10    0     2          ≤4          1.5     8
   Traumatic SDH + SAH + external ventricular drainage (EVD) (1)                       Meropenem               10    0     2          ≤4          0.5     8
   Traumatic EDH + SDH + craniotomy (1)                                                Ciprofloxacin            8    0     4          ≤1          1      16
   s/p craniotomy (1)                                                               MICs, minimum inhibitory concentration; S, susceptible; I, intermediate;
   Spontaneous ICH + EVD (1)                                                        R, resistant.
   Arteriovenous malformation + ICH + VP shunt (1)
   Aneurysm rupture + SAH + craniotomy +VP shunt (1)
                                                                                    (12/42) of ABM with polymicrobial infection. Among the
   Brain tumor + craniotomy ± VP shunt (2)
                                                                                    implicated Pseudomonas spp. of monomicrobial ABM, P.
   Chiari malformation + craniectomy (1)
                                                                                    aeruginosa was the most common, accounting for 86.2% (25/
   Nasopharyngeal carcinoma with skull base invasion (2)
                                                                                    29) of the cases. Of the 25 P. aeruginosa ABM cases, 72% (18/
   s/p VP shunt (2)
                                                                                    25) of the cases had a postneurosurgical state as the preced-
   brain tumor, craniopharyngioma, astrocytoma; s/p, post state.                    ing event. In Taiwan, except for Klebsiella pneumoniae ABM,
                                                                                    which is commonly seen in DM patients as a community-
antibiotics used for the treatment of these 12 cases were                           acquired, spontaneous infection (2,3), the high incidence of
ceftazidime for the six surviving cases, and ceftazidime (n =                       a postneurosurgical state as the preceding event is also com-
4), cefepime (n = 1) and meropenem (n = 1) for the other six                        mon in other Gram-negative forms of ABM (2,4). Therefore,
expired cases.                                                                      a positive culture result from the clinical specimens is the
   This study revealed that Pseudomonas spp. accounted                              only practical method for further confirmation of P. aeruginosa
for 8.3% (29/350) of monomicrobial ABM and for 28.6%                                ABM.

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   The high incidence of third-generation cephalosporin-                 susceptibility and appropriate clinical microbiological advice.
resistant Gram-negative pathogens isolated from CSF speci-               However, most of the P. aeruginosa ABM cases had complex
mens of ABM was previously reported in our study in 1999                 preceding postneurosurgical conditions which may interfere
(5). In that study, Acinetobacter baumannii was found to                 with the analysis of the morbidity and mortality of ABM.
be the most notorious pathogen, and the others were K.
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